A cognitive prosthesis for memory facilitation by closed-loop functional ensemble stimulation of hippocampal neurons in primate brain

Sam A. Deadwyler, Robert E. Hampson, Dong Song, Ioan Opris, Greg A. Gerhardt, Vasilis Z. Marmarelis, Theodore W. Berger

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Very productive collaborative investigations characterized how multineuron hippocampal ensembles recorded in nonhuman primates (NHPs) encode short-term memory necessary for successful performance in a delayed match to sample (DMS) task and utilized that information to devise a unique nonlinear multi-input multi-output (MIMO) memory prosthesis device to enhance short-term memory in real-time during task performance. Investigations have characterized how the hippocampus in primate brain encodes information in a multi-item, rule-controlled, delayed match to sample (DMS) task. The MIMO model was applied via closed loop feedback micro-current stimulation during the task via conformal electrode arrays and enhanced performance of the complex memory requirements. These findings clearly indicate detection of a means by which the hippocampus encodes information and transmits this information to other brain regions involved in memory processing. By employing the nonlinear dynamic multi-input/multi-output (MIMO) model, developed and adapted to hippocampal neural ensemble firing patterns derived from simultaneous recorded multi-neuron CA1 and CA3 activity, it was possible to extract information encoded in the Sample phase of DMS trials that was necessary for successful performance in the subsequent Match phase of the task. The extension of this MIMO model to online delivery of electrical stimulation patterns to the same recording loci that exhibited successful CA1 firing in the DMS Sample Phase provided the means to increase task performance on a trial-by-trial basis. Increased utility of the MIMO model as a memory prosthesis was exhibited by the demonstration of cumulative increases in DMS task performance with repeated MIMO stimulation over many sessions. These results, reported below in this article, provide the necessary demonstrations to further the feasibility of the MIMO model as a memory prosthesis to recover and/or enhance encoding of cognitive information in humans with memory disruptions resulting from brain injury, disease or aging.

Original languageEnglish
Pages (from-to)452-460
Number of pages9
JournalExperimental Neurology
StatePublished - Jan 1 2017

Bibliographical note

Funding Information:
The authors acknowledge the technical assistance of Joshua Long, Joseph Noto, Christina Dyson, Brian Parrish, Jeff Atwell, Michael Todd, and Lucas Santos, Ph.D. This work was supported by DARPA REMIND ( N66001-09-C-2080 to S.A.D ., N66001-09-C-2081 to T.W.B), and RAM (N66001-14-C-4016 ) Programs, G. Ling and J. Sanchez, Program Managers.

Publisher Copyright:
© 2016 Elsevier Inc.


  • Closed-loop
  • Electrical stimulation
  • Ensemble
  • Hippocampus
  • Memory
  • Neural prosthesis
  • Nonlinear model

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience


Dive into the research topics of 'A cognitive prosthesis for memory facilitation by closed-loop functional ensemble stimulation of hippocampal neurons in primate brain'. Together they form a unique fingerprint.

Cite this